Potent inhibition of specific diadenosine polyphosphate hydrolases by suramin

FEBS Letters

Rotllán, P¹  Rodrı́guez-Ferrer, C.R¹  Asensio, A.C¹  Oaknin, S¹ 

[1] Departamento de Bioquı́mica y Biologı́a Molecular, Universidad de La Laguna, E-38206 La Laguna, Tenerife, Canary Islands, Spain

关键词: Suramin;    Diadenosine tetraphosphate;    Diadenosine triphosphate;    Diadenosine tetraphosphate (asymmetrical) hydrolase;    Diadenosine triphosphate hydrolase;    Rat brain;    ApnA;    diadenosine 5′;    5‴-P1;    Pn-polyphosphates (n=2–6);    Ap3A;    diadenosine 5′;    5‴-P1;    P3-triphosphate;    Ap4A;    diadenosine 5′;    5‴-P1;    P4-tetraphosphate;    Ap5A;    diadenosine 5′;    5‴-P1;    P5-pentaphosphate;    Ap4;    adenosine 5′-tetraphosphate;    ϵ;    etheno;    ϵ-(ApnA);    di-(1;    N 6-ethenoadenosine) 5′;    5‴-P1;    Pn-polyphosphate;    ϵ-(Ap2A);    di-(1;    N 6-ethenoadenosine) 5′;    5‴P1;    P2-pyrophosphate;    ϵ-(Ap3A);    di-(1;    N 6-ethenoadenosine) 5′;    5‴-P1;    P2-triphosphate;    ϵ-(Ap4A);    di-(1;    N 6-ethenoadenosine) 5′;    5‴-P1;    P4-tetraphosphate;    ϵ-(Ap5A);    di-(1;    N 6-ethenoadenosine) 5′;    5‴-P1;    P5-pentaphosphate;    ϵ-Adenosine;    ϵ-AMP;    ϵ-ADP and ϵ-ATP refer to the 1;    N 6-etheno derivatives of adenosine;    AMP;    ADP and ATP;    respectively;    ApnAases;    diadenosine polyphosphate hydrolases;    Ap3Aase;    diadenosine triphosphate hydrolase (EC 3.6.1.29);    Ap4Aase;    asymmetrical diadenosine tetraphosphate hydrolase (EC 3.6.1.17);   

DOI  :  10.1016/S0014-5793(98)00579-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The cytosolic enzymes asymmetrical diadenosine tetraphosphate hydrolase (EC 3.6.1.17, Ap₄Aase) and diadenosine triphosphate hydrolase (EC 3.6.1.29, Ap₃Aase) are inhibited competitively by suramin. Ap₄Aase and Ap₃Aase were assayed in cytosolic rat brain extracts using fluorogenic analogues of the respective substrates diadenosine tetraphosphate (Ap₄A) and diadenosine triphosphate (Ap₃A). K _i values for suramin as inhibitor of Ap₄Aase and Ap₃Aase were 5×10⁻⁶ M and 3×10⁻⁷ M, respectively. Results indicate that suramin or suramin-like derivatives may be useful tools to investigate diadenosine polyphosphate cleaving enzymes and that the intracellular diadenosine polyphosphate metabolism may be a pharmacological target of suramin with biological and clinical implications.

【 授权许可】

Unknown